A Phase II Study of Chemo-Immunotherapy Followed by Durvalumab (MEDI4736) and Ceralasertib (AZD6738) in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Big Ten Cancer Research Consortium BTCRC-LUN18-363
Overview
- Phase
- Phase 2
- Intervention
- Cisplatin
- Conditions
- Extensive Stage Small Cell Lung Cancer
- Sponsor
- Muhammad Furqan
- Enrollment
- 30
- Locations
- 5
- Primary Endpoint
- Progression Free Survival (PFS)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
The primary objective of this single arm study is to estimate the progression free survival of previously-untreated patients with extensive stage small cell lung cancer. Patients will receive initial chemo-immunotherapy followed by maintenance therapy with durvalumab and oral ceralasertib.
Investigators
Muhammad Furqan
Clinical Associate Professor.
Big Ten Cancer Research Consortium
Eligibility Criteria
Inclusion Criteria
- •Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
- •Age \>= 18 years at the time of consent.
- •ECOG Performance Status of 0-1 within 14 days prior to registration (Appendix A of Protocol).
- •Histological or cytological confirmed small cell lung carcinoma
- •Extensive stage disease
- •Patient must be considered suitable to receive a platinum-based chemotherapy as 1st line treatment for ES-SCLC. Chemotherapy must contain either Carboplatin or Cisplatin in combination with Etoposide.
- •Measurable disease according to RECIST v1.1 for solid tumors within 28 days prior to registration.
- •Prior treatment must be completed within the following number of days prior to registration:
- •-Palliative radiation: for painful bony lesion must be completed prior to registration and recovered from significant bone marrow toxicity. For patients who received WBRT, 14 days washout is required prior to study therapy. Patient's must be off steroids without worsening of symptoms related to brain metastases. Patient should be on stable doses of anti-convulsant.
- •Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 14 days prior to registration
Exclusion Criteria
- •Prior systemic therapy for extensive stage or recurrent SCLC
- •Patients with recurrent SCLC, who received chemotherapy or definitive chest radiation in the past for limited-stage SCLC.
- •Clinically significant active infection requiring systemic therapy
- •Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
- •Participants who have undergone major surgery within 28 days before first dose of study drug
- •Participants who are currently receiving any other investigational agents
- •Active malignancy requiring therapy other than small cell lung cancer, excluding: non-melanoma skin cancer, noninvasive colonic polyps, superficial bladder tumors, cervical cancer in-situ, ductal carcinoma in situ of the breast, monoclonal B-cell lymphocytosis, or monoclonal gammopathy of undetermined significance.
- •Diagnosis of immunodeficiency or is receiving systemic steroid therapy (\> 10 mg of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to study enrolment. Patient's on physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Topical, inhaled or intra-articular steroids are not considered as systemic steroids. Steroids as premedication for hypersensitivity reaction (e.g. CT scan premedication) or prior to chemotherapy is allowed.
- •Active autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], systemic lupus erythematosus, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
- •Patients with vitiligo or alopecia
Arms & Interventions
Cisplatin or Carboplatin + Etoposide + Durvalumab + Ceralasertib
Initial Phase: Cycles 1-4 Cisplatin or Carboplatin: Day 1 Etoposide: Days 1-3 Durvalumab, 1500 mg: Day 1 q 3 weeks Maintenance Phase, Cycles 5+ Durvalumab, 1500 mg: Day 8 q 4 wks. Ceralasertib at 240mg po BID twice a day: Days 1-7
Intervention: Cisplatin
Cisplatin or Carboplatin + Etoposide + Durvalumab + Ceralasertib
Initial Phase: Cycles 1-4 Cisplatin or Carboplatin: Day 1 Etoposide: Days 1-3 Durvalumab, 1500 mg: Day 1 q 3 weeks Maintenance Phase, Cycles 5+ Durvalumab, 1500 mg: Day 8 q 4 wks. Ceralasertib at 240mg po BID twice a day: Days 1-7
Intervention: Carboplatin
Cisplatin or Carboplatin + Etoposide + Durvalumab + Ceralasertib
Initial Phase: Cycles 1-4 Cisplatin or Carboplatin: Day 1 Etoposide: Days 1-3 Durvalumab, 1500 mg: Day 1 q 3 weeks Maintenance Phase, Cycles 5+ Durvalumab, 1500 mg: Day 8 q 4 wks. Ceralasertib at 240mg po BID twice a day: Days 1-7
Intervention: Etoposide
Cisplatin or Carboplatin + Etoposide + Durvalumab + Ceralasertib
Initial Phase: Cycles 1-4 Cisplatin or Carboplatin: Day 1 Etoposide: Days 1-3 Durvalumab, 1500 mg: Day 1 q 3 weeks Maintenance Phase, Cycles 5+ Durvalumab, 1500 mg: Day 8 q 4 wks. Ceralasertib at 240mg po BID twice a day: Days 1-7
Intervention: Durvalumab
Cisplatin or Carboplatin + Etoposide + Durvalumab + Ceralasertib
Initial Phase: Cycles 1-4 Cisplatin or Carboplatin: Day 1 Etoposide: Days 1-3 Durvalumab, 1500 mg: Day 1 q 3 weeks Maintenance Phase, Cycles 5+ Durvalumab, 1500 mg: Day 8 q 4 wks. Ceralasertib at 240mg po BID twice a day: Days 1-7
Intervention: Ceralasertib
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: From enrollment until the time of disease progression, assessed for a maximum of 24 months
Progression free survival (PFS) is defined as the time from the initiation of treatment (C1D1) to the time when the criteria for disease progression is met as defined by RECIST v1.1 OR death due to any cause. The PFS is subject to right censoring due to loss to follow-up or at the end of study duration.
Secondary Outcomes
- Duration of Response(24 months)
- Overall Survival (OS)(24 months)
- Time to CNS Progression(From enrollment until the time of cns progression, assessed for a maximum of 24 months)
- Time to disease progression(From enrollment until the time of disease progression,assessed for a maximum of 24 months)
- Progression free survival for maintenance therapy(From Cycle 5, Day 1 of maintenance therapy until disease progression, assessed for a maximum of 19 months)
- Objective response rate (ORR)(24 months)
- Time to Systemic Progression(From enrollment until the time of systemic progression, assessed for a maximum of 24 months)
- Disease Control Rate(8 weeks from Cycle 1 Day 1)
- Toxicity Profile(24 months)